| First Author | Huang M | Year | 2022 |
| Journal | eNeuro | Volume | 9 |
| Issue | 6 | PubMed ID | 36635241 |
| Mgi Jnum | J:332555 | Mgi Id | MGI:7427116 |
| Doi | 10.1523/ENEURO.0247-22.2022 | Citation | Huang M, et al. (2022) Increase in Tau Pathology in P290S Mapt Knock-In Mice Crossed with App (NL-G-F) Mice. eNeuro 9(6):ENEURO.0247-22.2022 |
| abstractText | Alzheimer's Disease (AD) is characterized by the pathologic assembly of amyloid beta (Abeta) peptide, which deposits into extracellular plaques, and tau, which accumulates in intraneuronal inclusions. To investigate the link between Abeta and tau pathologies, experimental models featuring both pathologies are needed. We developed a mouse model featuring both tau and Abeta pathologies by knocking the P290S mutation into murine Mapt and crossing these Mapt (P290S) knock-in (KI) mice with the App (NL-G-F) KI line. Mapt (P290S) KI mice developed a small number of tau inclusions, which increased with age. The amount of tau pathology was significantly larger in App (NL-G-F) xMapt (P290S) KI mice from 18 months of age onward. Tau pathology was higher in limbic areas, including hippocampus, amygdala, and piriform/entorhinal cortex. We also observed AT100-positive and Gallyas-Braak-silver-positive dystrophic neurites containing assembled filamentous tau, as visualized by in situ electron microscopy. Using a cell-based tau seeding assay, we showed that Sarkosyl-insoluble brain extracts from both 18-month-old Mapt (P290S) KI and App (NL-G-F) xMapt (P290S) KI mice were seed competent, with brain extracts from double-KI mice seeding significantly more than those from the Mapt (P290S) KI mice. Finally, we showed that App (NL-G-F) xMapt (P290S) KI mice had neurodegeneration in the piriform cortex from 18 months of age. We suggest that App (NL-G-F) xMapt (P290S) KI mice provide a good model for studying the interactions of aggregation-prone tau, Abeta, neuritic plaques, neurodegeneration, and aging. |
